The Sloan Kettering Institute requests a SOLiD 3 sequencer. This instrument will be used by scientists to sequence whole or parts of genomes at incredible depth and with extreme accuracy. This instrument will enable various biological applications such as de novo sequencing, epigenomics, mutation detection, transcriptome profiling and metagenomics. The requested instrument will double the sequencing capability of the Sloan Kettering Institute and thereby reduce the turnaround time to 3 to 4 weeks (from 8 weeks currently). The SOLiD 3 methodology is based on sequential ligation with dye-labeled oligonucleotides. This technology advances biological research, particularly cancer research, with its incredibly high accuracy, ultra-high throughput capability and application flexibility. Each nucleotide is interrogated twice during sequencing. This technique reduces measurement errors and produces highly accurate sequence data suitable for the detection of sequence variation, including rare variants. NIH-supported major users include (1) Dr. Scott Keeney, who is studying the role of Spo11 in DNA double-strand breaks that initiate recombination;Dr. Eric Lai, who is using Drosophila as a model system to better understand the effect of Notch signaling and microRNAs on developmental patterning;and Dr. Samuel Singer, who is taking an integrative approach to characterize liposarcoma subtypes molecularly and biochemically. This instrument will also be supporting some more modest projects from investigators affiliated with all the programs in the Sloan Kettering institute: Cancer Biology and Genetics (Joan Massague), Molecular Biology (John Petrini), Immunology (Michael Glickman), Human Oncology and Pathogenesis (Charles Sawyers, David Solit, Ross Levine), and Developmental Biology (Kathryn Anderson, Mary Baylies). The SOLiD 3 sequencer will be located in the Genomics Core Laboratory of MSKCC. This microarray and DNA sequencing core facility has been directed by Dr. Agnes Viale since its inception 8 years ago. Public Health Relevance Statement: The requested instrument will be used by scientists at Memorial Sloan-Kettering Cancer Center to sequence genomes. This acquisition will greatly enhance the pace of these MSKCC research efforts.